台灣中部某醫學中心醫療照護相關之Methicillin抗藥性金黃色葡萄球菌感染率預測方法之探討－趨勢、抗生素使用量與抗藥性相關性及時間序列分析和分子生物分型

Abstract

Background: The importance of methicillin-resistant Staphylococcus aureus (MRSA) infection antimicrobial resistance has increased rapidly during the last 15 years and has become a global health issue. MRSA infections have an enormous impact on the mortality and morbidity in the hospital settings. Objectives: (1) Study 1: The objective of study 1 is to use the correlation between antimicrobial consumption and antimicrobial resistance and apply the forecasting models performed time series analysis to explain the relationship antimicrobial consumption, infection control measures and antibiotic resistance. (2) Study 2: The objective of study 2 is to use molecular typing techniques and to identify the most feasible methods for routine clinical setting to investigate MRSA isolates in a standard clinical laboratory. We also aimed to use the results of these molecular methods to characterize the MRSA strains isolated from health care workers (HCWs) and patients during an outbreak in a respiratory care ward in central Taiwan. Methods: (1) Study 1: We investigated the long-term impact of antibiotic use policy on the rates of consumption (expressed as daily-defined doses (DDD) per 1000 patient days (PD)) of various parenteral antibiotics, the prevalence of MRSA, and incidence of healthcare-associated MRSA (HA-MRSA, persons/1000 PD) infection at Chung Shan Medical University Hospital (CSMUH) from 2001 to 2009. Using time-series analysis based on monthly data during 6 year period (January 2004 to December 2009). The different antimicrobials consumption and alcohol-based hand rub were separately regressed to explore the relationship of incidence of healthcare-associated infection (HAI) and HA-MRSA (persons/1000 PD). Monthly alcohol-based hand rub consumption was expressed in liters/1000 PD. (2) Study 2: We used the methods include Pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), antibiograms derived from susceptibility testing of MRSA isolates, and multiplex PCR for detection of staphylococcal cassette chromosome (SCC)mec typing and Panton-Valentine leukocidin (pvl) gene typing to discriminate MRSA isolates. Results: (1) Study 1: During this time, the consumption of all antimicrobials for systemic use decreased by 33%. This change was driven by a 44% decrease in the consumption of the unrestricted antibacterials, which was offset by a 42% increase in the consumption of the restricted agents. The trends in MRSA prevalence (number of isolates per 1000 PD) and HA-MRSA incidence (number of HA-MRSA-infected persons per 1000 PD) correlated with the trend in overall consumption of the antimicrobials. Significant positive correlations were observed between MRSA prevalence and the consumption of extended-spectrum and β-lactamase-resistant penicillins, first-generation cephalosporins, macrolides, lincosamides, aminoglycosides, and glycopeptides. Significant positive correlations were found between the incidence of HA-MRSA infection and the consumption of tetracyclines, extended-spectrum and β-lactamase-resistant penicillins, sulfonamides and trimethoprim, macrolides, lincosamides, and aminoglycosides. The multivariate analysis showed that using alcohol-based hand rub for hand hygiene practice had a statistical significant effectiveness on the HAI (P = 0.0002) and HA-MRSA incidence (P = 0.0066). An increasing alcohol-based hand rub consumption was subsequently associated with reduce incidence of HAI and HA-MRSA incidence. In HA-MRSA incidence model showed that temporal increase in the use of third-generation cephalosporins (P = 0.0015) is, after a time lag of up to 4 months, followed by temporal increase in the incidence of HA-MRSA significantly. This model explained 39% of the monthly variations in the incidence of HA-MRSA. An increasing alcohol-based hand rub consumption of one liters/1000 PD are associated with decreasing 0.375 persons/1000 PD HA-MRSA Infection, after one month later. This model explained 27 % of the monthly variations in the incidence of HA-MRSA. (2) Study2: From March to June 2006, the incidence of MRSA infection increased 3.75-fold. The overall carrier rates among the HCWs were 31.3% (21/67, total S. aureus) and 16.4% (MRSA), and 14.9% (methicillin-sensitive SA, MSSA). PFGE, MLST, antibiograms derived from susceptibility testing of MRSA isolates, multiplex PCR typing and pvl gene typing provided strong epidemiologic and microbiologic evidence that an outbreak of MRSA infections at our hospital was linked to the same PFGE pulsotype A SCCmec type II, pvl negative, MLST ST5 strain of MRSA isolated from seven HCWs and five patients. The outbreak was controlled by application of topical fucidin ointment to the anterior nares by all HCWs colonized with MRSA. After one week’s treatment with fucidin ointment, follow-up cultures revealed no colonization by MRSA, and no new infections arose among the patients. Conclusions: (1) Study1: We have documented the ongoing successful reduction in total consumption of antimicrobials associated with a decrease in the incidence of HA-MRSA and prevalence of MRSA over a 9-year period. We successfully applied forecasting model to demonstrate the increase alcohol-based hand rub consumption was correlated with reduction the incidence of HAI and HA-MRSA, and reductions in individual restricted antimicrobials were significantly positively correlated with decreases in the incidence of HA-MRSA infections. (2) Study 2: We used molecular typing methods to investigate of an outbreak of MRSA infection in a respiratory care ward in Taiwan. We conclude that multiplex PCR is a feasible and useful method combination with PFGE for outbreak investigations in routine clinical laboratories.